Fungi belonging to the genus Candida are one of the most common causes of fungal infections worldwide.
Many species of Candida are harmless commensals or endosymbionts of their hosts, such as for example human beings.
Fungi belonging to the species Candida albicans and Candida tropicalis are normally present on the mucosa of oral cavity, gastro-intestinal tract and vagina. However, when the flora of the mucosae is altered, for example due to long treatment with antibiotics or hormonal changes, fungi can abnormally multiply and cause superficial infections, for example in the mouth or in the vagina, known as candidiasis. In immunosuppressed people, fungi can even cause severe systemic infections, known as candidemia, that are sometimes deadly.
Vulvovaginitis caused by fungi represents today about 30-35% of vaginal infections and is mostly caused by Candida albicans fungi.
Vulvovaginitis is accompanied by changes of the vaginal pH and the main symptoms are intense vaginal and/or vulvar itching, leakages, inflammation and pain.
Typically, the treatment is by administration of topical antimycotic drugs in form of creams, vaginal ovules and solutions for external use. In case of severe and/or relapsing infections, antimycotic drugs are administered orally.
Pevaryl™ is a commercially available cream for the treatment of vulvovaginal mycosis, containing 1% w/w of econazole nitrate.
Econazole is an imidazole derivative, endowed with a broad spectrum antimycotic activity and commonly used for the treatment of Candida albicans mycosis.
Several patent applications disclose combinations of active ingredients useful in the treatment of oral and vulvovaginal mycosis.
WO 96/26724 discloses a pharmaceutical composition comprising an anti-inflammatory amount of benzydamine or a salt thereof, an antimicrobially effective amount of an antimicrobial agent and a pharmaceutically acceptable carrier or excipient.
US 2009/0208558 relates to the use of an antimycotic agent and an epithelial cell or endothelial cell adhesion inhibitor for producing a combination drug for the topical treatment of Candida mycosis.
Most drug combinations show an additive effect. In some instances however, the combinations show less or more than an additive effect. These combinations are called antagonistic or synergistic, respectively. Antagonistic or synergistic effects are unpredictable, and are unexpected experimental findings. Finding highly efficacious combinations, i.e., synergistic mixtures, of active agents is challenging however. Serendipity is not a valid route as the number of potential combinations of agents is staggeringly large. The other normal discovery strategy of deducing potential combinations from knowledge of mechanism is also limited in its potential because many biological end points of living organisms are affected by multiple pathways. These pathways are often not known, and even when they are, the ways in which the pathways interact to produce the biological end effect are often unknown.